Photocatalytic direct borylation of carboxylic acids

The preparation of high value-added boronic acids from cheap and plentiful carboxylic acids is desirable. To date, the decarboxylative borylation of carboxylic acids is generally realized through the extra step synthesized redox-active ester intermediate or in situ generated carboxylic acid covalent derivatives above 150 °C reaction temperature. Here, we report a direct decarboxylative borylation method of carboxylic acids enabled by visible-light catalysis and that does not require any extra stoichiometric additives or synthesis steps. This operationally simple process produces CO2 and proceeds under mild reaction conditions, in terms of high step economy and good functional group compatibility. A guanidine-based biomimetic active decarboxylative mechanism is proposed and rationalized by mechanistic studies. The methodology reported herein should see broad application extending beyond borylation.


General Information
All available compounds were purchased from commercial suppliers and were used without further purification unless otherwise noted.
Flash column chromatography and preparative thin-layer chromatography were performed on silica gel; Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was performed on an ACQUITY UPLC H-Class PLUS instrument equipped with a Waters PDA eλ Detector and a Waters Acquity QDA mass spectrometer. Highresolution mass spectroscopy was performed on a Bruker Fourier Transform Ion Cyclotron Resonance Mass Spectrometer. Fluorescence spectra were measured on an F-7000 spectrophotometer. (Hitachi, Japan) Unless otherwise noted, all reactions were carried out under an air atmosphere in screw-capped vials. A LED (30 W, λ max = 440 nm) may be shared by 14 screw-capped vials for irradiation obtained from Xuzhou Aijia Electronic Technology Co., LTD. In each case, each LED was set up, and the light source was placed ~2 cm from the reaction vessels (Fig. 1). A box was placed over the lights to shield the light. The reaction temperature was measured using a contact thermometer to be 35 °C.

Procedure for Optimization Studies
A 5 mL vial equipped with a magnetic stir bar was charged with 3-acetylcarboxylic acid (16.5 mg, 0.1 mmol), photocatalyst, [Co] catalyst, borylated reagent, or other additives; the anhydrous solvent was then into the vial. The reaction mixture was stirred without irradiation for 10 min at ambient temperature, and then a guanidine-based reagent was gradually added to the vial under stirring. The reaction mixture was stirred without irradiation for another 10 min at ambient temperature and then irradiated for 24 h while maintaining the temperature at approximately 35 °C through cooling with a fan. 1,3,5-trimethoxybenzene (HPLC internal standard quantification based on the standard internal 1,3,5-trimethoxybenzene, the peak area and relative correction factor of reaction product) was added then the mixture was analyzed by HPLC.   The NMR data were in consistent with the reported data 2 .
it was obtained as white solid (

Control Experiment
Following the above same condition but only without Co(dmgH) 2 pyCl, or

Stern-Volmer Quenching Experiment
The quenching rate k q was determined using the Stern-Volmer relationship:

Synthesis and conversion of the intermediate R-Co(III)
PhCo(dmgH) 2 py was synthesized according to literature. 15

Radical Trapping or Inhibiting Experiments
Following the standard borylated condition with TEMPO (31 mg, 0.2 mmol), the 2ai' was acquired with a 10% yield, and no 2n was detected.
Following the above same radical inhibiting experiments without TMG, no 2n and the captured product of TEMPO 2n' were detected. 3. The absorbance of the resulting solution in a quartz cuvette (l = 1.0 cm) at 510 nm was measured by a UV-Vis spectrometer. A non-irradiated sample and other samples with 5s, 15s, 30s, 45s, 60s, and 90s irradiation time were also prepared, and the absorbance at 510 nm was measured.

Condition 1: A 5 mL vial equipped with a magnetic stir bar was charged
The amount of ferrous ion formed was calculated as follows:  The value of the slope collected is 5.32 × 10 -8 ; division by the known quantum yield Φ = 0.845 yields a photon flux of 6.3×10 -8 einsteins s -1 .

Determination of the Reaction Quantum Yield
To a 4 mL a quartz cuvette equipped with a magnetic stir bar was charged

Computational Study
All density functional theory (DFT) calculations were carried out with the

Calculation of redox potential
The redox potentials were obtained from the computation of oxidationreduction half-reactions, according to Where ∆G is the free energy change (J/mol), n is the number of electrons transfer in oxidation-reduction half-reaction, F = 96485 J mol -1 V -1 is the Faraday constant, is the oxidation-reduction half-reactions' potential. (SCE) is the potential of Saturated Calomel Electrode.
The Gibbs free energies were computed through the DFT and TDDFT calculation with frequency analysis.

Discussion
The computation data above does tell the effects of TMG, which is lowering the redox potential of benzoic acid to 1a/1c for about 1.12V/1.15V, and the effects of photo-inducing by lowering the redox potential of [

Calculation of the activation energy of the redox reaction
According to Marcus theory, the energy barrier of the reaction, i.e. the activation energy can be calculated as following: Where 0 is the reorganization energy and ∆ 0 is the energy change of reaction. 0 and ∆ 0 can be calculated from adiabatic state energies at the optimized structure of the initial and final states. Because of the complexity to treat the whole redox reaction with the donor-acceptor complex, we computed the two half reactions separately first, and then combined the results to get the approximate result. (showed in The computed results shown above once again confirms that TMG group is essential to promote the redox reaction, by lowering both ΔG 0 (thermodynamics) and ΔG ‡ (kinetics). In particular, the ΔG ‡ of the [Ir-1] IV 1a/1c redox reaction is much smaller than the ones of [Ir-7] IV (0.76/2.80 kcal/mol vs 9.46/13.53 kcal/mol), agreeing well with the big difference of yield between these two catalysts.
Since the rate of proton transfer (1a to 1c) is fast, and the reverse proton transfer (1c to 1a) rate is also fast, at ground state 1a and 1c could reach a Boltzmann distribution first, and then proceed the redox reaction. According to the low activation energy of both redox paths (0.76 kcal/mol for 1a, 2.80 kcal/mol for 1c) and the limitation of computational accuracy, we conclude that Oxidation-HAT process and PT-Oxidation process could both contribute to the TMG-assisted benzoic acid oxidation reaction effectively.

Molecular orbital analyses on radical forming
To further understand the role of TMG to reduce the redox potential, we compare the involved molecular orbitals (MOs) of the benzoic acid and benzoic acid-TMG complex.
From the comparison of the MOs, it is clear that the main difference comes from the Singly-Occupied MOs (SOMOs) for the corresponding radical. For complex 1a and 1c, the SOMO is much delocalized to the TMG molecules, and the orbital energies are decreased comparing to the one of isolated benzoic acid.   According to the data above, complex 1a,1a-1 are able to form, and then proceed proton transfer to form 1c, 1c-1 respectively. There is only small structure and energy difference between 1a-1,1c-1 and 1a,1c, caused by the rotation of the TMG group.

Supplementary
Since the redox potential of 1a, 1c (1.39V, 1.36V) are both lower than those of 1a-1, 1c-1 (1.46V, 1.40V), implying more improvement caused by TMG. We picked 1a, 1c as the representatives of the mechanism in our research.
For complex 1a-2 and 1a-3, they are not easy to form because of their positive binding energy.